Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases

Tempe K Chen; Jagmohan S Batra; David E Michalik; Jacqueline Casillas; Ramesh Patel; Maritza E Ruiz; Harneet Hara; Bhavita Patel; Meena Kadapakkam; James Ch'Ng; Catherine B Small; Panagiotis Zagaliotis; Carolyn E Ragsdale; Luis O Leal; Emmanuel Roilides; Thomas J Walsh

doi:10.1093/ofid/ofac535

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases

Open Forum Infect Dis. 2022 Oct 11;9(11):ofac535. doi: 10.1093/ofid/ofac535. eCollection 2022 Nov.

Authors

Tempe K Chen^{1

2}, Jagmohan S Batra^{1

2}, David E Michalik^{1

2}, Jacqueline Casillas^{3

4}, Ramesh Patel^{3

4}, Maritza E Ruiz^{3

4}, Harneet Hara^{3

4}, Bhavita Patel^{3

4}, Meena Kadapakkam^{3

4}, James Ch'Ng^{3

4}, Catherine B Small⁵, Panagiotis Zagaliotis^{5

6

7}, Carolyn E Ragsdale⁸, Luis O Leal⁸, Emmanuel Roilides⁶, Thomas J Walsh^{5

9}

Affiliations

¹ Department of Pediatric Infectious Diseases, MemorialCare Miller Children's & Women's Hospital Long Beach, Long Beach, California, USA.
² Department of Pediatrics, Division of Infectious Diseases, University of California Irvine School of Medicine, Irvine, California, USA.
³ Department of Pediatric Hematology/Oncology, MemorialCare Miller Children's & Women's Hospital Long Beach, Long Beach, California, USA.
⁴ Division of Hematology/Oncology, Department of Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA.
⁵ Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medicine, New York, New York, USA.
⁶ Infectious Diseases Unit, 3rd Department of Pediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece.
⁷ Department of Pharmacology and Therapeutics, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁸ Partner Therapeutics, Inc., Lexington, Massachusetts, USA.
⁹ Center for Innovative Therapeutics and Diagnostics, Richmond, Virginia, USA.

Abstract

Background: Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs).

Methods: The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted.

Results: Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response).

Conclusions: Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.

Keywords: antifungal agents; fungal diseases; granulocyte-macrophage colony-stimulating factor; immune modulation; sargramostim.